Mutations in the Wolfram syndrome type 1 gene (WFS1) define a clinical entity of dominant low-frequency sensorineural hearing loss.
نویسندگان
چکیده
OBJECTIVE To describe low-frequency sensorineural hearing loss (LFSNHL) inherited as a dominant trait in 3 families and in 1 sporadic case. DESIGN Longitudinal clinical study from 1968 to 2001. SETTING Tertiary care hospital; field studies conducted by molecular genetic research laboratory. PARTICIPANTS Dominant LFSNHL families. INTERVENTIONS Questionnaires, serial audiograms, and interviews, correlated with molecular genetic data. OUTCOME MEASURES Symptoms, age of onset, serial audiometric data, and hearing aid use. RESULTS Low-frequency sensorineural hearing loss is typically diagnosed in the first decade and slowly progresses over decades; LFSNHL is often asymptomatic in young patients, few of whom use hearing aids. Speech perception becomes affected in later decades when patients develop high-frequency loss. Even children with a strong family history of dominant LFSNHL were not monitored routinely. Penetrance appears complete in that all individuals with a genetic mutation developed hearing loss. CONCLUSIONS Dominant LFSNHL is most commonly caused by mutations in the Wolfram syndrome type 1 gene (WFS1). Mutations in WFS1 also cause a rare recessive syndromic form of hearing loss known as Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Routine newborn hearing screening methods will not typically identify hearing loss affecting frequencies below 2000 Hz; thus, children at risk must be specifically monitored. Genetic counseling and genetic testing may be useful in the management of patients with this type of hearing loss.
منابع مشابه
WFS1 mutation screening in a large series of Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis
A heterozygous mutation in the Wolfram syndrome type 1 gene (WFS1) causes autosomal dominant nonsyndromic hereditary hearing loss, DFNA6/14/38, or Wolfram-like syndrome. To date, more than 40 different mutations have been reported to be responsible for DFNA6/14/38. In the present study, WFS1 variants were screened in a large series of Japanese hearing loss (HL) patients to clarify the prevalenc...
متن کاملA PCR-RFLP assay for the A716T mutation in the WFS1 gene, a common cause of low-frequency sensorineural hearing loss.
Nonsyndromic low-frequency sensorineural hearing loss (LFSNHL) is an unusual type of hearing loss that affects frequencies at 2,000 Hz and below. Recently, we reported five different heterozygous missense mutations in the Wolfram syndrome gene, WFS1, found to be responsible for LFSNHL in six families. One of the five mutations, A716T, may be a common cause of LFSNHL, as it has been reported in ...
متن کاملProgression of low-frequency sensorineural hearing loss (DFNA6/14-WFS1).
OBJECTIVE To assess the audiometric profile and speech recognition characteristics in affected members of 2 families with DFNA6/14 harboring heterozygous mutations in the WFS1 gene that cause an autosomal dominant nonsyndromic sensorineural hearing impairment trait. DESIGN Family study. SETTING Tertiary referral center. Patients Thirteen patients from 2 recently identified Dutch families wi...
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Optic atrophy (OA) and sensorineural hearing loss (SNHL) are key abnormalities in several syndromes, including the recessively inherited Wolfram syndrome, caused by mutations in WFS1. In contrast, the association of autosomal dominant OA and SNHL without other phenotypic abnormalities is rare, and almost exclusively attributed to mutations in the Optic Atrophy-1 gene (OPA1), most commonly the p...
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Wolfram-like syndrome (WFSL) is a rare autosomal dominant disease characterised by congenital progressive hearing loss, diabetes mellitus, and optic atrophy. The patient was a boy with the juvenile form of diabetes mellitus and findings which clinically matched the symptoms of Wolfram syndrome. At the age of 3 1/4 years, diabetes mellitus was diagnosed in this boy who also had severe psychomoto...
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ورودعنوان ژورنال:
- Archives of otolaryngology--head & neck surgery
دوره 129 4 شماره
صفحات -
تاریخ انتشار 2003